Polymorphisms In The Chemokines And Their Receptors Genes And Risk Of Myocardial Infarction

Objective:Chemokine ligands and their receptors are increasingly recognized to be key mediators in inflammatory processes that underlie the pathogenesis of atherosclerosis. Currently, CCL5, CCL2and their receptors (CCR5, CCR2) have already been proposed as candidate genes for studies of genetic markers in myocardial infarction (MI). Here we were to assess the possible association between variations in these genes and susceptibility to MI in the Chinese Han population in a case-control study.Methods:Genotypes of patients with MI (n=634) were compared to controls (n=601). The CCL5rs2107538(-403G/A), CCL2rs1024611(-2518A/G), CCR5rs333(A32ins/del), and CCR2rs1799864(190G/A) gene polymorphisms were evaluated in1235individuals by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) mapping, and genotypes of several individuals were confirmed by the DNA sequence analysis.Results:No subject was found for CCR5-A32allele in present study. No association was established between CCL2rs1024611and CCR2rs1799864polymorphisms and MI. Concerning CCL5rs2107538polymorphism, the A allele occurred at a higher frequency in patients with MI than in control subjects. Furthermore, the A/A genotype of CCL5rs2107538associated with a significantly increased risk of MI, independently of conventional cardiovascular risk factors (OR=3.346,95%CI=1.938-5.775, P<0.01, A/A vs. G/G). Further analysis showed that MI patients had significantly more A-403-A-2518haplotype (CCL5-403G/A/CCL2-2518A/G,21.8%vs.26.6%, OR=1.230,95%CI=1.012-1.493, P=0.038) and AA/AA genotype (CCL5-403G/A/CCL2-2518A/G,5.0%vs.12.1%, OR=3.245,95%CI=1.780-5.914, P<0.01).Conclusion:Although the data do not support an association between CCL2rs1024611, CCR2rs1799864and CCR5rs333polymorphisms and MI, the genetic variation in CCL5gene may be a useful genetic marker for determining susceptibility to MI in the Chinese Han population.